Diagnosing and treating acute coronary syndromes (ACS) is unlike
diagnosing and treating frank myocardial infarction (MI) because the
underlying pathophysiology of the two conditions differs.

Dr. Hal Chadow, director of the Division of Cardiology at the
Brookdale Hospital and Medical Center and assistant professor of
medicine at SUNY Brooklyn, explains that atherosclerotic plaque
is more complicated than just an accumulation of low-density lipoprotein.
It also contains smooth muscle cells and fat-rich macro-phages called
foam cells. The finding in the Physicians Health Study that men
with higher levels of C-reactive protein, a marker of inflammation,
had a higher risk of myocardial infarction demonstrated the importance
of the inflammatory component to atherosclerotic plaque.

In a standard MI, plaque grows large enough to occlude a major
coronary artery, cutting off blood flow and oxygen to myocardium
and resulting in extensive ischemia and muscle death. This generally
occurs when arterial stenosis reaches 90 percent. In ACS the ischemic
process occurs through a different mechanism. Structurally, atherosclerotic
plaque essentially consists of a lipid core covered by a fibrous
cap. When some hypothesized "trigger" makes the plaque unstable,
the fibrous cap ruptures and exposes blood flowing through the coronary
arterial circulation to a very thrombogenic core. Simultaneous activation
of the coagulation cascade and endothelial injury activates platelets,
producing a thrombus that is carried downstream and clogs smaller
vessels. What triggers an atherosclerotic plaque to rupture is unclear,
Dr. Chadow says.

Support for this model, says Dr. Chadow, comes from the observation
that if you do an angiogram and find an artery with a 30 percent
stenosis and another artery with a 90 percent stenosis, and that
patient has an MI in six to 24 months, two-thirds of the time the
artery with the 30 percent lesion was the culprit infarct-related
vessel. "And that is the lesion that you would do nothing about,"
he points out. Since myocardial damage from a thrombus is not as
sudden and extensive as with occlusion, CK-MB might not rise enough
to turn positive and the ECG might not show ST-segment elevation.
But substantial necrosis of heart muscle cells occurs nonetheless,
though perhaps at a slower rate.

Dr. Paul Heidenreich, assistant professor of medicine at Stanford
University School of Medicine and director of echocardiography at
the Palo Alto VA Health Care System, calls ST elevation a marker
of occlusive thrombus, where the myocardium is dying as each minute
goes by. In ACS, there may be an intermittently obstructive thrombus,
which is usually platelet-rich and nonocclusive and doesn't produce
ST elevation.

Treatment for the two conditions also differs. In frank MI, the
goal is to open the artery. Fibrinolytic therapy, such as thrombolysis
with tPA or streptokinase, is ideal in this context. In ACS, on
the other hand, tPA may actually worsen outcomes. In these patients
the goal is to dissolve the platelet-rich thrombus with anti-platelet
agents, such as glycoprotein IIb/IIIa inhibitors.

To prevent MIs, it would be useful to be able to identify so-called
vulnerable plaques, those with a high propensity for rupture. Research
has shown that a plaque with a thin fibrous cap is more likely to
rupture, and smooth muscle cells produce degradative proteins called
metalloproteinases that digest the fibrous cap and make it more
vulnerable to rupture. In addition, lipid-lowering therapy with
statins can convert a vulnerable plaque to a stable plaque. Attempts
to distinguish vulnerable from stable plaques with magnetic resonance
imaging and other imaging modalities are underway, but they are
in their "infancy," in Dr. Chadow's view.